Nanoscintillator-Mediated X-Ray Induced Photodynamic Therapy for Deep-Seated Tumors: From Concept to Biomedical Applications

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Abstract

Photodynamic therapy (PDT) has shown great effectiveness in oncotherapy but has not been implemented in broad clinical applications because the limited penetration depth of the light used has been unable to reach deep-seated tumors. However, X-rays have been widely used in the clinical field for imaging and radiation therapy due to their excellent tissue penetration depth. Recently, X-rays have been established as an ideal excitation source for PDT, which holds great promise for breaking the depth limitation of traditional PDT for treatment of deep-seated tumors. This review aims to provide an overview of nanoscintillator-mediated X-ray induced PDT (X-PDT) including the concept, the design considerations of nanosensitizers for X-PDT, the modelling of nanosensitizer energy deposition, the putative mechanism by which X-PDT kills cells, and the prospects of future directions. We attempt to summarize the main developments that have occurred over the past decades. Possibilities and challenges for the clinical translation of X-PDT are also discussed.

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Most cited references 56

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All-inorganic perovskite nanocrystal scintillators

Angelo All, Qiushui Chen, Jing Wu … (2018)

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Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.

Twan Lammers, Fabian Kiessling, Wim E Hennink … (2012)

Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells, active drug targeting to endothelial cells and triggered drug delivery. Significant progress has been made in this area of research both at the preclinical and at the clinical level, and a number of (primarily passively tumor-targeted) nanomedicine formulations have been approved for clinical use. Significant progress has also been made with regard to better understanding the (patho-) physiological principles of drug targeting to tumors. This has led to the identification of several important pitfalls in tumor-targeted drug delivery, including I) overinterpretation of the EPR effect; II) poor tumor and tissue penetration of nanomedicines; III) misunderstanding of the potential usefulness of active drug targeting; IV) irrational formulation design, based on materials which are too complex and not broadly applicable; V) insufficient incorporation of nanomedicine formulations in clinically relevant combination regimens; VI) negligence of the notion that the highest medical need relates to metastasis, and not to solid tumor treatment; VII) insufficient integration of non-invasive imaging techniques and theranostics, which could be used to personalize nanomedicine-based therapeutic interventions; and VIII) lack of (efficacy analyses in) proper animal models, which are physiologically more relevant and more predictive for the clinical situation. These insights strongly suggest that besides making ever more nanomedicine formulations, future efforts should also address some of the conceptual drawbacks of drug targeting to tumors, and that strategies should be developed to overcome these shortcomings. Copyright © 2011 Elsevier B.V. All rights reserved.

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Self-Assembled Copper-Amino Acid Nanoparticles for In Situ Glutathione “AND” H2O2 Sequentially Triggered Chemodynamic Therapy

Baojin Ma, Shu R. Wang, Feng. Liu … (2018)

Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minimal invasiveness and high specificity. In this study, we demonstrate self-assembled copper-amino acid mercaptide nanoparticles (Cu-Cys NPs) for in situ glutathione-activated and H2O2-reinforced chemodynamic therapy for drug-resistant breast cancer. After endocytosis into tumor cells, the Cu-Cys NPs could first react with local GSH, induce GSH depletion, and reduce Cu2+ to Cu+. Subsequently, the generated Cu+ would react with local H2O2 to generate toxic hydroxyl radicals (·OH) via a Fenton-like reaction, which has a fast reaction rate in the weakly acidic TME, that are responsible for tumor-cell apoptosis. Due to the high GSH and H2O2 concentration in tumor cells, which sequentially triggers the redox reactions, Cu-Cys NPs exhibited relatively high cytotoxicity to cancer cells, whereas normal cells were left alive. The in vivo results also proved that Cu-Cys NPs efficiently inhibited drug-resistant breast cancer without causing obvious systemic toxicity. As a novel copper mercaptide nanoformulation responsive to the TME, these Cu-Cys NPs may have great potential in chemodynamic cancer therapy.

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Author and article information

Journal

Journal ID (nlm-ta): Theranostics

Journal ID (iso-abbrev): Theranostics

Journal ID (publisher-id): thno

Title: Theranostics

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1838-7640

Publication date Collection: 2020

Publication date (Electronic): 1 January 2020

Volume: 10

Issue: 3

Pages: 1296-1318

Affiliations

[1 ]State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China

[2 ]Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States

[3 ]Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, United States

Author notes

✉ Corresponding authors: Email: shawn.chen@ 123456nih.gov (X. C.), hchen@ 123456xmu.edu.cn (H. C.)

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: thnov10p1296

DOI: 10.7150/thno.41578

PMC ID: 6956812

PubMed ID: 31938066

SO-VID: 30c8add8-eeef-4815-93a2-66afd6b9be9a

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This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Nanoscintillator-Mediated X-Ray Induced Photodynamic Therapy for Deep-Seated Tumors: From Concept to Biomedical Applications

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Abstract

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Electrospinning for biomedical applications

Most cited references 56

All-inorganic perovskite nanocrystal scintillators

Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.

Self-Assembled Copper-Amino Acid Nanoparticles for In Situ Glutathione “AND” H2O2 Sequentially Triggered Chemodynamic Therapy

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